Skip to main content
SpringerLink
Log in

Epigenetic Imprinting of Immunological Memory

  • Chapter
  • First Online:
Epigenetics - A Different Way of Looking at Genetics

Part of the book series: Epigenetics and Human Health ((EHH))

Abstract

A hallmark of the immune system is its memory for antigens it has previously encountered. The cellular basis of immunological memory is memory B and T lymphocytes. In particular, memory T helper (Th) lymphocytes express the specific antigen receptors and are epigenetically imprinted for expression of distinct genes, which mediate more effective immune response during rechallenges. The functional program of a memory Th cell is established through T cell receptor (TCR) engagement, in conjunction with instructive signals provided during its primary activation, leading to the induction of so-called lineage-specifying transcription factors which initiate the functional program by epigenetic modifications. Upon reencounter of the antigen, the functional program is recalled quickly by TCR signaling and independently of the original instructive signal. In this review, we will summarize current knowledge of epigenetic imprinting of memory Th1, Th2, and interleukin 10 (IL-10)-producing Th cells, if any, with a focus on the role of lineage-specifying transcription factors and DNA methylation.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Afkarian M et al (2002) T-bet is a STAT1-induced regulator of IL-12R expression in naive CD4+ T cells. Nat Immunol 3(6):549–557

    Article  CAS  PubMed  Google Scholar 

  • Agarwal S, Avni O, Rao A (2000) Cell-type-restricted binding of the transcription factor NFAT to a distal IL-4 enhancer in vivo. Immunity 12(6):643–652

    Article  CAS  PubMed  Google Scholar 

  • Ahmed R, Gray D (1996) Immunological memory and protective immunity: understanding their relation. Science 272(5258):54–60

    Article  CAS  PubMed  Google Scholar 

  • Anderson CF et al (2007) CD4(+)CD25(-)Foxp3(-) Th1 cells are the source of IL-10-mediated immune suppression in chronic cutaneous leishmaniasis. J Exp Med 204(2):285–297

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ansel KM et al (2006) Regulation of Th2 differentiation and Il4 locus accessibility. Annu Rev Immunol 24:607–656

    Article  CAS  PubMed  Google Scholar 

  • Avni O et al (2002) T(H) cell differentiation is accompanied by dynamic changes in histone acetylation of cytokine genes. Nat Immunol 3(7):643–651

    CAS  PubMed  Google Scholar 

  • Ben-Sasson SZ et al (2001) Cell division is not a “clock” measuring acquisition of competence to produce IFN-gamma or IL-4. J Immunol 166(1):112–120

    Article  CAS  PubMed  Google Scholar 

  • Bird A (2002) DNA methylation patterns and epigenetic memory. Genes Dev 16(1):6–21

    Article  CAS  PubMed  Google Scholar 

  • Bird JJ et al (1998) Helper T cell differentiation is controlled by the cell cycle. Immunity 9(2):229–237

    Article  CAS  PubMed  Google Scholar 

  • Bix M, Locksley RM (1998) Independent and epigenetic regulation of the interleukin-4 alleles in CD4+ T cells. Science 281(5381):1352–1354

    Article  CAS  PubMed  Google Scholar 

  • Chang H-D et al (2007) Expression of IL-10 in Th memory lymphocytes is conditional on IL-12 or IL-4, unless the IL-10 gene is imprinted by GATA-3. Eur J Immunol 37(3):807–817

    Article  CAS  PubMed  Google Scholar 

  • Ding W et al (2003) Altered cutaneous immune parameters in transgenic mice overexpressing viral IL-10 in the epidermis. J Clin Invest 111(12):1923–1931

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Djuretic IM et al (2007) Transcription factors T-bet and Runx3 cooperate to activate Ifng and silence Il4 in T helper type 1 cells. Nat Immunol 8(2):145–153

    Article  CAS  PubMed  Google Scholar 

  • Dong J et al (2007) IL-10 is excluded from the functional cytokine memory of human CD4+ memory T lymphocytes. J Immunol 179(4):2389–2396

    Article  CAS  PubMed  Google Scholar 

  • Dong J et al (2013) Loss of methylation at the IFNG promoter and CNS-1 is associated with the development of functional IFN-gamma memory in human CD4(+) T lymphocytes. Eur J Immunol 43(3):793–804

    Article  CAS  PubMed  Google Scholar 

  • Elo LL et al (2010) Genome-wide profiling of interleukin-4 and STAT6 transcription factor regulation of human Th2 cell programming. Immunity 32(6):852–862

    Article  CAS  PubMed  Google Scholar 

  • Fields PE, Kim ST, Flavell RA (2002) Cutting edge: changes in histone acetylation at the IL-4 and IFN-gamma loci accompany Th1/Th2 differentiation. J Immunol 169(2):647–650

    Article  CAS  PubMed  Google Scholar 

  • Fields PE et al (2004) Th2-specific chromatin remodeling and enhancer activity in the Th2 cytokine locus control region. Immunity 21(6):865–876

    Article  CAS  PubMed  Google Scholar 

  • Finotto S et al (2002) Development of spontaneous airway changes consistent with human asthma in mice lacking T-bet. Science 295(5553):336–338

    Article  CAS  PubMed  Google Scholar 

  • Garrity PA et al (1994) Interleukin-2 transcription is regulated in vivo at the level of coordinated binding of both constitutive and regulated factors. Mol Cell Biol 14(3):2159–2169

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gavrilescu LC et al (2004) STAT1 is essential for antimicrobial effector function but dispensable for gamma interferon production during Toxoplasma gondii infection. Infect Immun 72(3):1257–1264

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Grogan JL et al (2001) Early transcription and silencing of cytokine genes underlie polarization of T helper cell subsets. Immunity 14(3):205–215

    Article  CAS  PubMed  Google Scholar 

  • Grunig G et al (1997) Interleukin-10 is a natural suppressor of cytokine production and inflammation in a murine model of allergic bronchopulmonary aspergillosis. J Exp Med 185(6):1089–1099

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Harrington LE et al (2008) Memory CD4 T cells emerge from effector T-cell progenitors. Nature 452(7185):356–360

    Article  CAS  PubMed  Google Scholar 

  • Hatton RD et al (2006) A distal conserved sequence element controls Ifng gene expression by T cells and NK cells. Immunity 25(5):717–729

    Article  CAS  PubMed  Google Scholar 

  • Henkel G, Brown MA (1994) PU.1 and GATA: components of a mast cell-specific interleukin 4 intronic enhancer. Proc Natl Acad Sci U S A 91(16):7737–7741

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hoffmann KF, Cheever AW, Wynn TA (2000) IL-10 and the dangers of immune polarization: excessive type 1 and type 2 cytokine responses induce distinct forms of lethal immunopathology in murine schistosomiasis. J Immunol 164(12):6406–6416

    Article  CAS  PubMed  Google Scholar 

  • Hogan PG et al (2003) Transcriptional regulation by calcium, calcineurin, and NFAT. Genes Dev 17(18):2205–2232

    Article  CAS  PubMed  Google Scholar 

  • Hollander GA et al (1998) Monoallelic expression of the interleukin-2 locus. Science 279(5359):2118–2121

    Article  CAS  PubMed  Google Scholar 

  • Hosokawa H et al (2013) Functionally distinct Gata3/Chd4 complexes coordinately establish T helper 2 (Th2) cell identity. Proc Natl Acad Sci U S A 110(12):4691–4696

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hu-Li J et al (2001) Regulation of expression of IL-4 alleles: analysis using a chimeric GFP/IL-4 gene. Immunity 14(1):1–11

    Article  CAS  PubMed  Google Scholar 

  • Hutchins AS et al (2002) Gene silencing quantitatively controls the function of a developmental trans-activator. Mol Cell 10(1):81–91

    Article  CAS  PubMed  Google Scholar 

  • Hwang ES et al (2005) T helper cell fate specified by kinase-mediated interaction of T-bet with GATA-3. Science 307(5708):430–433

    Article  CAS  PubMed  Google Scholar 

  • Im SH et al (2004) Chromatin-level regulation of the IL10 gene in T cells. J Biol Chem 279(45):46818–46825

    Article  CAS  PubMed  Google Scholar 

  • Jankovic D et al (2007) Conventional T-bet(+)Foxp3(-) Th1 cells are the major source of host-protective regulatory IL-10 during intracellular protozoan infection. J Exp Med 204(2):273–283

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jones EA, Flavell RA (2005) Distal enhancer elements transcribe intergenic RNA in the IL-10 family gene cluster. J Immunol 175(11):7437–7446

    Article  CAS  PubMed  Google Scholar 

  • Kaplan MH et al (1996) Impaired IL-12 responses and enhanced development of Th2 cells in Stat4-deficient mice. Nature 382(6587):174–177

    Article  CAS  PubMed  Google Scholar 

  • Kemper C et al (2003) Activation of human CD4+ cells with CD3 and CD46 induces a T-regulatory cell 1 phenotype. Nature 421(6921):388–392

    Article  CAS  PubMed  Google Scholar 

  • Kishikawa H et al (2001) The cell type-specific expression of the murine IL-13 gene is regulated by GATA-3. J Immunol 167(8):4414–4420

    Article  CAS  PubMed  Google Scholar 

  • Kock J et al (2014) Nuclear factor of activated T cells regulates the expression of interleukin-4 in Th2 cells in an all-or-none fashion. J Biol Chem 289(39):26752–26761

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Kuhn R et al (1993) Interleukin-10-deficient mice develop chronic enterocolitis. Cell 75(2):263–274

    Article  CAS  PubMed  Google Scholar 

  • Lang R et al (2002) Autocrine deactivation of macrophages in transgenic mice constitutively overexpressing IL-10 under control of the human CD68 promoter. J Immunol 168(7):3402–3411

    Article  CAS  PubMed  Google Scholar 

  • Lavenu-Bombled C et al (2002) Interleukin-13 gene expression is regulated by GATA-3 in T cells: role of a critical association of a GATA and two GATG motifs. J Biol Chem 277(21):18313–18321

    Article  CAS  PubMed  Google Scholar 

  • Lee DU, Rao A (2004) Molecular analysis of a locus control region in the T helper 2 cytokine gene cluster: a target for STAT6 but not GATA3. Proc Natl Acad Sci U S A 101(45):16010–16015

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lee HJ et al (2000) GATA-3 induces T helper cell type 2 (Th2) cytokine expression and chromatin remodeling in committed Th1 cells. J Exp Med 192(1):105–115

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lee DU, Agarwal S, Rao A (2002) Th2 lineage commitment and efficient IL-4 production involves extended demethylation of the IL-4 gene. Immunity 16(5):649–660

    Article  CAS  PubMed  Google Scholar 

  • Lee GR et al (2003) Regulation of the Th2 cytokine locus by a locus control region. Immunity 19(1):145–153

    Article  CAS  PubMed  Google Scholar 

  • Lieberman LA et al (2004) STAT1 plays a critical role in the regulation of antimicrobial effector mechanisms, but not in the development of Th1-type responses during toxoplasmosis. J Immunol 172(1):457–463

    Article  CAS  PubMed  Google Scholar 

  • Lighvani AA et al (2001) T-bet is rapidly induced by interferon-gamma in lymphoid and myeloid cells. Proc Natl Acad Sci U S A 98(26):15137–15142

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lohning M, Richter A, Radbruch A (2002) Cytokine memory of T helper lymphocytes. Adv Immunol 80:115–181

    Article  CAS  PubMed  Google Scholar 

  • Lohning M et al (2003) Establishment of memory for IL-10 expression in developing T helper 2 cells requires repetitive IL-4 costimulation and does not impair proliferation. Proc Natl Acad Sci U S A 100(21):12307–12312

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Lohning M et al (2008) Long-lived virus-reactive memory T cells generated from purified cytokine-secreting T helper type 1 and type 2 effectors. J Exp Med 205(1):53–61

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Macatonia SE et al (1993) Dendritic cells and macrophages are required for Th1 development of CD4+ T cells from alpha beta TCR transgenic mice: IL-12 substitution for macrophages to stimulate IFN-gamma production is IFN-gamma-dependent. Int Immunol 5(9):1119–1128

    Article  CAS  PubMed  Google Scholar 

  • Mazzoni A et al (2015) Demethylation of the RORC2 and IL17A in human CD4+ T lymphocytes defines Th17 origin of nonclassic Th1 cells. J Immunol 194(7):3116–3126

    Article  CAS  PubMed  Google Scholar 

  • Melvin AJ et al (1995) Hypomethylation of the interferon-gamma gene correlates with its expression by primary T-lineage cells. Eur J Immunol 25(2):426–430

    Article  CAS  PubMed  Google Scholar 

  • Mikovits JA et al (1998) Infection with human immunodeficiency virus type 1 upregulates DNA methyltransferase, resulting in de novo methylation of the gamma interferon (IFN-gamma) promoter and subsequent downregulation of IFN-gamma production. Mol Cell Biol 18(9):5166–5177

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Moore KW et al (2001) Interleukin-10 and the interleukin-10 receptor. Annu Rev Immunol 19:683–765

    Article  CAS  PubMed  Google Scholar 

  • Morinobu A et al (2002) STAT4 serine phosphorylation is critical for IL-12-induced IFN-gamma production but not for cell proliferation. Proc Natl Acad Sci U S A 99(19):12281–12286

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mosmann TR et al (1986) Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins. J Immunol 136(7):2348–2357

    CAS  PubMed  Google Scholar 

  • Mullen AC et al (2001) Role of T-bet in commitment of TH1 cells before IL-12-dependent selection. Science 292(5523):1907–1910

    Article  CAS  PubMed  Google Scholar 

  • Mullen AC et al (2002) Hlx is induced by and genetically interacts with T-bet to promote heritable T(H)1 gene induction. Nat Immunol 3(7):652–658

    CAS  PubMed  Google Scholar 

  • Murray PJ et al (1997) T cell-derived IL-10 antagonizes macrophage function in mycobacterial infection. J Immunol 158(1):315–321

    CAS  PubMed  Google Scholar 

  • Nawijn MC et al (2001) Enforced expression of GATA-3 in transgenic mice inhibits Th1 differentiation and induces the formation of a T1/ST2-expressing Th2-committed T cell compartment in vivo. J Immunol 167(2):724–732

    Article  CAS  PubMed  Google Scholar 

  • Neumann C et al (2014) Role of Blimp-1 in programing Th effector cells into IL-10 producers. J Exp Med 211(9):1807–1819

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • O’Garra A, Vieira P (2007) T(H)1 cells control themselves by producing interleukin-10. Nat Rev Immunol 7(6):425–428

    Article  PubMed  CAS  Google Scholar 

  • Okamura H et al (2000) Concerted dephosphorylation of the transcription factor NFAT1 induces a conformational switch that regulates transcriptional activity. Mol Cell 6(3):539–550

    Article  CAS  PubMed  Google Scholar 

  • Ouyang W et al (1998) Inhibition of Th1 development mediated by GATA-3 through an IL-4-independent mechanism. Immunity 9(5):745–755

    Article  CAS  PubMed  Google Scholar 

  • Ouyang W et al (2000) Stat6-independent GATA-3 autoactivation directs IL-4-independent Th2 development and commitment. Immunity 12(1):27–37

    Article  CAS  PubMed  Google Scholar 

  • Pai SY, Truitt ML, Ho IC (2004) GATA-3 deficiency abrogates the development and maintenance of T helper type 2 cells. Proc Natl Acad Sci U S A 101(7):1993–1998

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Park AY, Hondowicz BD, Scott P (2000) IL-12 is required to maintain a Th1 response during Leishmania major infection. J Immunol 165(2):896–902

    Article  CAS  PubMed  Google Scholar 

  • Peng SL et al (2001) NFATc1 and NFATc2 together control both T and B cell activation and differentiation. Immunity 14(1):13–20

    Article  CAS  PubMed  Google Scholar 

  • Pinderski LJ et al (2002) Overexpression of interleukin-10 by activated T lymphocytes inhibits atherosclerosis in LDL receptor-deficient Mice by altering lymphocyte and macrophage phenotypes. Circ Res 90(10):1064–1071

    Article  CAS  PubMed  Google Scholar 

  • Podtschaske M et al (2007) Digital NFATc2 activation per cell transforms graded T cell receptor activation into an all-or-none IL-2 expression. PLoS One 2(9), e935

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Riviere I, Sunshine MJ, Littman DR (1998) Regulation of IL-4 expression by activation of individual alleles. Immunity 9(2):217–228

    Article  CAS  PubMed  Google Scholar 

  • Rogge L et al (1997) Selective expression of an interleukin-12 receptor component by human T helper 1 cells. J Exp Med 185(5):825–831

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rutz S et al (2008) Notch regulates IL-10 production by T helper 1 cells. Proc Natl Acad Sci U S A 105(9):3497–3502

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Saraiva M et al (2009) Interleukin-10 production by Th1 cells requires interleukin-12-induced STAT4 transcription factor and ERK MAP kinase activation by high antigen dose. Immunity 31(2):209–219

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schulz EG et al (2009) Sequential polarization and imprinting of type 1 T helper lymphocytes by interferon-gamma and interleukin-12. Immunity 30(5):673–683

    Article  CAS  PubMed  Google Scholar 

  • Seder RA et al (1993) Interleukin 12 acts directly on CD4+ T cells to enhance priming for interferon gamma production and diminishes interleukin 4 inhibition of such priming. Proc Natl Acad Sci U S A 90(21):10188–10192

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Siegel MD et al (1995) Activation of the interleukin-5 promoter by cAMP in murine EL-4 cells requires the GATA-3 and CLE0 elements. J Biol Chem 270(41):24548–24555

    Article  CAS  PubMed  Google Scholar 

  • Skapenko A et al (2004) GATA-3 in human T cell helper type 2 development. J Exp Med 199(3):423–428

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Stobie L et al (2000) The role of antigen and IL-12 in sustaining Th1 memory cells in vivo: IL-12 is required to maintain memory/effector Th1 cells sufficient to mediate protection to an infectious parasite challenge. Proc Natl Acad Sci U S A 97(15):8427–8432

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sun J et al (2009) Effector T cells control lung inflammation during acute influenza virus infection by producing IL-10. Nat Med 15(3):277–284

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Szabo SJ et al (1997) Regulation of the interleukin (IL)-12R beta 2 subunit expression in developing T helper 1 (Th1) and Th2 cells. J Exp Med 185(5):817–824

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Szabo SJ et al (2000) A novel transcription factor, T-bet, directs Th1 lineage commitment. Cell 100(6):655–669

    Article  CAS  PubMed  Google Scholar 

  • Szabo SJ et al (2002) Distinct effects of T-bet in TH1 lineage commitment and IFN-gamma production in CD4 and CD8 T cells. Science 295(5553):338–342

    Article  CAS  PubMed  Google Scholar 

  • Takemoto N et al (2000) Cutting edge: chromatin remodeling at the IL-4/IL-13 intergenic regulatory region for Th2-specific cytokine gene cluster. J Immunol 165(12):6687–6691

    Article  CAS  PubMed  Google Scholar 

  • Thierfelder WE et al (1996) Requirement for Stat4 in interleukin-12-mediated responses of natural killer and T cells. Nature 382(6587):171–174

    Article  CAS  PubMed  Google Scholar 

  • Thieu VT et al (2008) Signal transducer and activator of transcription 4 is required for the transcription factor T-bet to promote T helper 1 cell-fate determination. Immunity 29(5):679–690

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tykocinski LO et al (2005) A critical control element for interleukin-4 memory expression in T helper lymphocytes. J Biol Chem 280(31):28177–28185

    Article  CAS  PubMed  Google Scholar 

  • Usui T et al (2006) T-bet regulates Th1 responses through essential effects on GATA-3 function rather than on IFNG gene acetylation and transcription. J Exp Med 203(3):755–766

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Vahedi G et al (2013) Helper T-cell identity and evolution of differential transcriptomes and epigenomes. Immunol Rev 252(1):24–40

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Wang X, Mosmann T (2001) In vivo priming of CD4 T cells that produce interleukin (IL)-2 but not IL-4 or interferon (IFN)-gamma, and can subsequently differentiate into IL-4- or IFN-gamma-secreting cells. J Exp Med 194(8):1069–1080

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wei L et al (2010) Discrete roles of STAT4 and STAT6 transcription factors in tuning epigenetic modifications and transcription during T helper cell differentiation. Immunity 32(6):840–851

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wei G et al (2011) Genome-wide analyses of transcription factor GATA3-mediated gene regulation in distinct T cell types. Immunity 35(2):299–311

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wilson CB, Rowell E, Sekimata M (2009) Epigenetic control of T-helper-cell differentiation. Nat Rev Immunol 9(2):91–105

    Article  CAS  PubMed  Google Scholar 

  • Wurster AL, Pazin MJ (2008) BRG1-mediated chromatin remodeling regulates differentiation and gene expression of T helper cells. Mol Cell Biol 28(24):7274–7285

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yagi R et al (2010) The transcription factor GATA3 actively represses RUNX3 protein-regulated production of interferon-gamma. Immunity 32(4):507–517

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yamashita M et al (2002) Identification of a conserved GATA3 response element upstream proximal from the interleukin-13 gene locus. J Biol Chem 277(44):42399–42408

    Article  CAS  PubMed  Google Scholar 

  • Yamashita M et al (2004) Essential role of GATA3 for the maintenance of type 2 helper T (Th2) cytokine production and chromatin remodeling at the Th2 cytokine gene loci. J Biol Chem 279(26):26983–26990

    Article  CAS  PubMed  Google Scholar 

  • Yang Y et al (2007) Identification of a distant T-bet enhancer responsive to IL-12/Stat4 and IFNgamma/Stat1 signals. Blood 110(7):2494–2500

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yap G, Pesin M, Sher A (2000) Cutting edge: IL-12 is required for the maintenance of IFN-gamma production in T cells mediating chronic resistance to the intracellular pathogen, Toxoplasma gondii. J Immunol 165(2):628–631

    Article  CAS  PubMed  Google Scholar 

  • Zhang WX, Yang SY (2000) Cloning and characterization of a new member of the T-box gene family. Genomics 70(1):41–48

    Article  CAS  PubMed  Google Scholar 

  • Zheng W, Flavell RA (1997) The transcription factor GATA-3 is necessary and sufficient for Th2 cytokine gene expression in CD4 T cells. Cell 89(4):587–596

    Article  CAS  PubMed  Google Scholar 

  • Zhu J et al (2004) Conditional deletion of Gata3 shows its essential function in T(H)1-T(H)2 responses. Nat Immunol 5(11):1157–1165

    Article  CAS  PubMed  Google Scholar 

  • Zhu J et al (2012) The transcription factor T-bet is induced by multiple pathways and prevents an endogenous Th2 cell program during Th1 cell responses. Immunity 37(4):660–673

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhu J, Yamane H, Paul WE (2010) Differentiation of effector CD4 T cell populations (*). Annu Rev Immunol 28:445–489

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zuany-Amorim C et al (1995) Interleukin-10 inhibits antigen-induced cellular recruitment into the airways of sensitized mice. J Clin Invest 95(6):2644–2651

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgments

This work was funded by ERC-2010-AdG, 268987.

Author information

Authors and Affiliations

  1. Cell Biology, Deutsches Rheumaforschungszentrum Berlin (DRFZ), Institute of the Leibniz Association, Charitéplatz 1, 10117, Berlin, Germany

    Jun Dong, Hyun-Dong Chang & Andreas Radbruch

  2. Charité Universitätsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Germany

    Andreas Radbruch

Authors
  1. Jun Dong
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hyun-Dong Chang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Andreas Radbruch
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jun Dong .

Editor information

Editors and Affiliations

  1. Universität Erlangen, Institut für Klinische und molekulare Vi, Erlangen, Germany

    Walter Doerfler

  2. Biozentrum Köln, Universität zu Köln, Köln, Germany

    Petra Böhm

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Dong, J., Chang, HD., Radbruch, A. (2016). Epigenetic Imprinting of Immunological Memory. In: Doerfler, W., Böhm, P. (eds) Epigenetics - A Different Way of Looking at Genetics. Epigenetics and Human Health. Springer, Cham. https://doi.org/10.1007/978-3-319-27186-6_4

Download citation

Publish with us

Policies and ethics

Search

Navigation